The long-term goal of this project is to elucidate the molecular mechanisms of photoreceptor excitation and degeneration using single-step Drosophila mutants isolated for this purpose. Because evidence uncovered during the current project period suggests that the mechanisms of photoreceptor excitation and degeneration are closely related, mutations affecting both processes will be investigated. These mutations define at least 25 genes. Double mutants will be constructed in pairwise combinations to identify a subfamily of interdependent genes among the 25 genes being tested. Detailed genetic, electrophysiological, and morphological analyses will be carried out on the mutants identified by the double mutant studies. Attempts will be made to clone at least one, and hopefully as many as three, genes during the proposed project period. One of the main objectives of isolating these genes is to probe the human genome for homologous sequences. This may be one of the very few viable approaches for isolating human genes involved in photoreceptor degeneration presently available. In addition, additional mutations will be isolated in the ninaE gene, the presumptive R1-6 opsin structural gene, and these mutations will be investigated in detail to carry out structure-function analyses on the gene at the molecular level.